Functional nucleic acids with synthetic sugar or nucleobase moieties

Functional nucleic acids including aptamers and DNAzymes are a class of valuable molecular tool for biotechnology. However, DNA and RNA aptamers and catalysts suffer from low biological stability and limited chemical diversity. Xeno-nucleic acids (XNAs) refer to nucleic acid analogues containing sugar moieties that are structurally distinct from DNA and RNA and possess advantageous properties. In this article, we first focus on two types of XNAs, threose nucleic acid (TNA) and 2’-fluoroarabinose nucleic acid (FANA), and summarize recent in vitro selections of TNA and FANA aptamers and catalysts. We then review three classes of unnatural base pairs (UBPs) and highlight examples of UBP-containing DNA aptamers and DNAzymes. Lastly, we briefly describe an XNA-modified DNAzyme 10–23 (X10-23) and its application in RNA knockdown and virus detection. Functional XNAs provide important chemical biology tools for biomedical research and future interdisciplinary collaboration will boost XNA basic research and clinical translation.